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The vision-screening program for 3.5-year-old children in Japan consists of 3 steps:questionnaires and home visual acuity testing, visual acuity testing by nurses and inspection by medical officers at regional Public Health Centers, and examinations by ophthalmologists. In this study, we tested refraction with a hand-held autorefractometer in addition to visual acuity testing and inspection to reveal whether or not autorefraction leads to better detection of eye problems. Autorefraction was performed in 6 consecutive sessions by a single examiner in 265 children at 3.5 years of age who all visited the same center. The children were sent to the third step of examinations by ophthalmologists based on refractive error criteria:3 diopters myopia or 1 diopter hyperopia, and/or 2 diopters astigmatism in either eye, in addition to the current criteria:1) failure in either eye for 0.5 visual acuity at the center, 2) eye-related symptoms revealed by the questionnaires, or 3) eye problems detected by medical officers. Notices to visit ophthalmologists were issued for 64 children (24%), and 37 of those (58%) made the visits, so that documents containing final diagnoses were sent back to the Public Health Office. Of the 64 children, 12 were sent to ophthalmologists based on the current criteria only, 10 based on both the current criteria and the refractive error criteria, and 42 based on the refractive error criteria only. Twelve of the 13 children visiting ophthalmologists by the current criteria had diagnoses such as amblyopia and strabismus. In contrast, 15 of 24 children visiting ophthalmologists by only the refractive error criteria had mainly diagnoses of refractive errors, with no serious problems. In conclusion, autorefraction in addition to visual acuity testing and inspection led to detection of only one additional case of an eye disease at 3.5 years, while tripling the number of children sending to the third-step examination by an ophthalmologist. Thus, from a cost-effectiveness standpoint, autorefraction is not recommended as an additional test when the current system is conducted as designed.

We present a middle-aged, heterosexual Japanese man with mixed infections including human intestinal spirochetosis, which led us to the detection of human immunodeficiency virus (HIV) infection. The patient had syphilis without related physical or neurological findings. An examination for the serum antibody for HIV performed 9 years previously was negative. In a complete medical checkup at the present time, human intestinal spirochetosis and unspecified entamebic cysts were suggested by histological examination of colonic biopsy material and parasitic examination of the intestinal fluid, respectively. Moreover, a serological test for the antibody for HIV was positive. In specimens obtained by colonoscopy, Brachyspira aalborgi was diagnosed by ultrastructural study and the polymerase chain reaction method for bacterial 16S ribosomal deoxyribonucleic acid. Although HIV infection remains at low prevalence in Japan, we recommend examination for HIV infection in patients with human intestinal spirochetosis, especially when other co-infections are apparent.

For patients with acute myocardial infarction (MI), the immediate therapeutic goal is to establish the patency of the infarct-related artery. Prolonged myocardial ischemia, however, often breaks down the coronary microvasculature, and the flow to the infarct myocardium may be markedly reduced. This is called the no-reflow phenomenon. This phenomenon is important not solely because it correlates with infarct size but because it provides additional prognostic information. With recent advances in imaging modalities, the no-reflow phenomenon is observed more frequently than when clinical judgment alone is used. Patients with this phenomenon are associated with poor functional and clinical outcomes. Now, the no-reflow phenomenon can be a parameter with which to predict high-risk patients. The focus of reperfusion therapy has shifted toward the improvement of myocardial perfusion. The improvement of myocardial perfusion could promote the functional recovery of viable muscle and reduce infarct expansion, which is associated with favorable clinical outcomes. For this purpose, pharmacological interventions and catheter-based devices to retrieve embolic materials have been proposed. Advances in our understanding of the pathophysiology of microvascular dysfunction would aid the development of therapeutic strategies for its prevention and treatment.

Toremifene citrate is expected to prevent drug resistance in cancer patients by inhibiting p-glycoprotein activity. The safety and efficacy of combination therapy with high-dose toremifene citrate and paclitaxel were investigated. Between December 2003 and June 2004, 15 women with a mean age of 53 years old with metastatic breast cancer were enrolled. The administration schedule was 80mg/m2 of paclitaxel given on Days 1, 8, and 15, and 120mg/day of toremifene citrate orally administered starting on Day 18. On Days 32 and 39, paclitaxel was concurrently administered again. Toxicities, response rate, and time to treatment failure were assessed. All patients had been treated with endocrine or chemotherapy. Grade 3 leukopenia occurred in 2 patients on the administration of paclitaxel alone, and grade 3 febrile neutropenia occurred in 1 patient given the combination therapy. There was no grade 3 or greater non-hematological toxicity. There was no complete response and 1 partial response, producing a response rate of 6.7%. Median time to treatment failure was 2.7 months. Combination therapy of paclitaxel and toremifene was safe and well tolerated with minimal toxicity. Further clinical trials targeting patients with functional p-glycoprotein are warranted.

The annual number of suicides in Japan increased sharply in 1998, and since that time it has consistently exceeded 30,000 per year. In this study, we analyze a database of personal and background characteristics of 824 cases (605 men, 219 women) who completed suicide in Okayama Prefecture in 2002 and 2003. The data were obtained with cooperation from the police. Using the methodologies in a previous European study as a model, we classified the suicide methods into 8 categories. To examine the generational and regional differences in the choice of methods, we stratified the sample into 4 age groups (<-24, 2544, 4564, and >-65) and 2 regional groups (Okayama/Kurashiki vs. other areas). Our results on gender differences in 7 of the suicide methods were mostly similar to the European data. However, our data showed a remarkably higher proportionate male-to-female mortality ratio for poisoning by other substances (ICD-10, X65-X69 codes) (1.83, 1.15-2.92). In terms of generational differences in the choice of suicide methods, the Mantel-Haenszel test of homogeneity was significant for most of the categories in our study, suggesting an impact of age on how people commit suicide. There were no remarkable regional differences in our sample. An epidemic curve for suicides via carbon monoxide poisoning using charcoal briquets revealed a trend of time clustering not observed in the other 6 means. The database constructed and used in this study contains richer information than conventional death statistics and is expected to provide helpful knowledge and insights for future epidemiological studies.

This retrospective study assessed the radiographic results of 16 patients with avascular necrosis following treatment for developmental dislocation of the hip (DDH) who were subsequently treated between 1991 and 2005 by rotation acetabular osteotomy (RAO) combined with femoral intertrochan-teric osteotomy (FIO). Initial treatment was by Pavlik harness, cast fixation, or overhead traction. The parameters that showed consistent improvement were the index of centralization, the index of acetabular coverage, adequate reduction of the greater trochanter, and abductor sufficiency. The combined procedure appears to be effective in cases in which preoperative planning shows a reasonable expectation of congruency and osteoarthritis is limited to the early stages.

A 23-year old woman with acute biphenotypic leukemia (ABL) complained of chest pain with cough, high fever and hemoptysis during induction chemotherapy, although she had been treated with anti-biotics and micafungin. We made a clinical diagnosis of invasive pulmonary aspergillosis (IPA) based on a consolidation in the right upper lung field on a chest radiograph as well as a high level of serum beta-D-glucan (with no evidence of tuberculosis and candidiasis). We changed her treatment from micafungin to voriconazole. Later, we discovered an air-crescent sign by CT scan that supported the diagnosis of IPA. Following voriconazole treatment, clinical symptoms ceased and abnormal chest shadows improved gradually and concurrently with a recovery of neutrophils. IPA must be considered in immunocompromised patients with pulmonary infiltrates who do not respond to broad-spectrum antibiotics. Serological tests and CT findings can aid in early diagnosis of IPA, which, along with treatment for IPA, will improve clinical outcomes.

Interaction between the receptor for advanced glycation end products (RAGE) and its ligands has been implicated in the pathogenesis of various inflammatory disorders. In this study, we establish an in vitro binding assay in which recombinant human high-mobility group box 1 (rhHMGB1) or recombinant human S100A12 (rhS100A12) immobilized on the microplate binds to recombinant soluble RAGE (rsRAGE). The rsRAGE binding to both rhHMGB1 and rhS100A12 was saturable and dependent on the immobilized ligands. The binding of rsRAGE to rhS100A12 depended on Ca2 and Zn2, whereas that to rhHMGB1 was not. Scatchard plot analysis showed that rsRAGE had higher affinity for rhHMGB1 than for rhS100A12. rsRAGE was demonstrated to bind to heparin, and rhS100A12, in the presence of Ca2, was also found to bind to heparin. We examined the effects of heparin preparations with different molecular sizesunfractionated native heparin (UFH), low molecular weight heparin (LMWH) 5000Da, and LMWH 3000Da on the binding of rsRAGE to rhHMGB1 and rhS100A12. All 3 preparations concentration-dependently inhibited the binding of rsRAGE to rhHMGB1 to a greater extent than did rhS100A12. These results suggested that heparin's anti-inflammatory effects can be partly explained by its blocking of the interaction between HMGB1 or S100A12 and RAGE. On the other hand, heparin would be a promising effective remedy against RAGE-related inflammatory disorders.

Trimebutine at low concentrations (6 X 10(-9)-1.4 X 10(-8) M) slightly enhanced the twitch response of isolated guinea pig ileum induced by transmural stimulation. At high concentrations (2 X 10(-8)-2 X 10(-7) M), however, it inhibited the twitch response in a dose dependent manner. This inhibitory effect of trimebutine was reversed by naloxone (8.1 X 10(-9) M). These results suggest that trimebutine has an opiate-like action on the myenteric plexus.

A 67-year-old male patient initially showed memory disturbance followed by tremors a year later. The symptoms rapidly aggravated to dementia and Parkinsonian symptoms, and the patient died 2 years and 6 months after the onset at the age of 69 years and 5 months. Autopsy revealed numerous senile plaques in the cerebral cortex and Alzheimer's neurofibrillary tangles in the inferior temporal lobe and hippocampus. A number of Lewy bodies were found in the cerebral cortex and brain stem. Lewy bodies were found abundantly in the third layer of the pyramidal cells in the gyrus parahippocamalis. The distribution of Lewy bodies in the cerebral cortex was similar to that of inflated cells in Pick's disease.

An ultrafiltration method employing a Centrifree filter for determining the unbound fraction of estradiol was studied. Centrifugation was performed under conditions similar to those in vivo. Good correlation was recognized between this method and the equilibrium dialysis. This method was employed to determine the unbound fraction of estradiol in the serum and the peritoneal fluid of 26 infertility patients classified according to their menstrual dates. The total estradiol and progesterone contents in the peritoneal fluid were high after ovulation. There was no significant difference in the percentage of unbound estradiol in the serum among various groups. In the peritoneal fluid, however, the percentage of unbound estradiol for the day 12-14 patients was 4.5 +/- 0.2% in contrast with 3.8 +/- 0.4% for the day 15-18 group (p less than 0.05) and 3.5 +/- 0.1% (p less than 0.05) for the day 19-28 group. Moreover, the fraction (4.5%) of unbound estradiol in the peritoneal fluid of a patient with luteinized unruptured follicle (LUF) syndrome was comparable with that of patients in the follicular phase. The difference between the percentage of unbound estradiol in the peritoneal fluid before and after ovulation is considered to be due to the transudation of follicular estradiol in the follicular phase and the exudation of estradiol from the corpus luteum into the peritoneal cavity in the luteal phase.

The apparatus to measure multi-point critical flicker fusion frequency (MCFF) was devised for more precise determination of the critical flicker fusion frequency (CFF). Using this apparatus, the variations in flicker value after the work load of the television (TV) game, the Kraepelin using the video display terminal (VDT-Kraepelin) and the paper-Kraepelin were examined in order to test its practical applicability. The following results were obtained. The degree of decrease in the CFF values of some peripheral eye fields was larger than that on the central field of both eyes (ordinary CFF) after work load. The variation rates of the central and the peripheral flicker values were measured before and after loading in each work, and the correlations of variation rates between two CFF values among them were calculated. The numbers of peripheral eye fields showing significant correlation of variation rates between two eye fields in the TV game and the VDT-Kraepelin, were greater than those in the paper-Kraepelin.

The involvement of macrophages in the induction of metallothionein (MT) synthesis by bacterial endotoxin was studied in vitro. Rat peritoneal macrophages were incubated with endotoxin. The incubation medium from endotoxin-activated macrophages accelerated MT synthesis by human hepatic Chang cells. However, the incubation medium from non-activated macrophages did not. Endotoxin added to the culture medium of Chang cells was ineffective in inducing MT synthesis. The contents of zinc, copper and cadmium, which are primary inducers of MT, in the incubation medium of macrophages in the presence of endotoxin were not different from those in the absence of endotoxin. These results suggest that MT synthesis is induced by endotoxin-treated macrophages.

Protective effects of clinically used drugs against adriamycin (ADM)-induced toxicity were studied in ICR mice. The control mice, which were administered 15 mg/kg of ADM twice, survived 7.48 +/- 1.99 days (mean +/- S.D.). The survival times of mice treated with the following drugs, expressed as a percent of that of the control group, were 293.6% for coenzyme Q10 (Co Q10, 2 mg/kg), 402.2% for dextran sulfate (MDS, 300 mg/kg), 121.6% for flavin adenine dinucleotide (20 mg/kg), 236.3% for adenosine triphosphate disodium (50 mg/kg), 213.7% for reduced glutathione (100 mg/kg), 121.6% for phytonadione (50 mg/kg), 155.2% for inositol nicotinate (Ino-N, 500 mg/kg), 335.5% for nicomol (1000 mg/kg), 157.5% for nicardipine (10 mg/kg) and 123.3% for dipyridamol (50 mg/kg). Anti-hyperlipemic agents such as MDS, nicomol, Ino-N and Co Q10 strongly protected against the ADM-induced toxicity, and the mice administered these drugs lived significantly longer than the control mice. The mechanism of the protective effect was discussed.

Metaplastic bony tissue along with hyperplastic mucosal epithelium showing no atypism was detected in biopsy materials from a Yamada type I gastric polyp. The tissue was metaplastic woven bone associated with calcification. Histogenesis of the bone formation is as yet unknown. This is the first reported case of the presence of metaplastic bone accompanied by hyperplastic gastric mucosa so far.

Human peripheral blood mononuclear cells (PBM) were separated into sheep erythrocyte rosette-forming (Es+) and non Es+ cells by the Ficoll-Hypaque gradient sedimentation method. Thirty-eight percent of the Es+ cells formed rosettes with dog erythrocytes and were designated as Es+Ed+ cells. The remaining Es+ cells were designated as Es+Ed- cells. Only a few non Es+ cells formed rosettes with dog erythrocytes. Among Es+Ed+ cells, T4 antigen-positive cells were observed approximately 1.7 times as often as T8 antigen-positive cells, when measured by staining with OKT4 or OKT8 monoclonal antibody. Among Es+Ed- cells, however, T4 and T8 antigen-positive cells were observed in almost equal proportion. Preincubation of PBM with OKT11 monoclonal antibody, but not with OKT4 monoclonal antibody, inhibited the rosette formation with dog as well as sheep erythrocytes. These results indicated that Es+Ed+ cells were a subpopulation of T-cells in which a majority of the cells were T4 antigen-positive, and that the binding sites of dog erythrocytes on human T-cells was closely linked with that of sheep erythrocytes.

Temporal bone histopathological findings of two patients with trisomy 18 syndrome are described. Many of the abnormalities previously described were seen in the present cases; namely, atresia of the external auditory canal, aberrant course of the tensor tympani muscle, malformed stapes, aberrant course of the facial nerve with an obtuse angulation at the first genu and displacement of geniculate ganglion cells into the internal auditory canal, shortened cochlea with decreased spiral ganglion cell population, and vestibular anomalies, such as bony and membranous blockage of the superior semicircular canal. Moreover, an extremely underdeveloped malleus and incus continuous with a persistent Meckel's cartilage were observed.

Effects of afferent stimulation of the lingual nerve (LNAS) on gastrointestinal motility and the reflex pathways which mediate the response to LNAS were investigated in rats. LNAS induced excitatory, inhibitory or biphasic responses in the stomach, duodenum and proximal colon. These responses continued after bilateral vagotomy, but were abolished after additional bilateral splanchnicotomy or transection of the spinal cord between Th4 and Th5. The inhibitory, excitatory and biphasic responses induced by LNAS were not affected by decerebration. Both after administration of atropine (0.2 mg/kg, i.v.) and guanethidine (3-5 mg/kg, i.v.), LNAS-induced excitatory and inhibitory responses were abolished in most cases, but the slight inhibitory response in the stomach and duodenum to LNAS remained in a few cases. These results suggest that the reflex centers which cause LNAS-induced excitatory and inhibitory responses are located in the dorsal nucleus of vagus and that the reflex pathways include the vagus and splanchnic nerves.

Six pregnant women with convulsions between 25 to 40 weeks of gestation were experienced. Among them, 4 patients were diagnosed as having intracranial hemorrhage and two as simple eclampsia. With the aid of brain CT scan, one case of arteriovenous malformation was detected and treated surgically with good prognosis for both the mother and the fetus. Two patients were diagnosed to have cerebral hemorrhage with subsequent penetration into the lateral ventricles and were treated conservatively. Their fetuses were delivered alive by cesarean section, but the mothers expired. The other patient with cerebral hemorrhage was treated surgically, and both the mother and the fetus survived. One of the simple eclampsia patients was noted to have a growth retarded fetus at 32 weeks of pregnancy with subsequent intra-uterine death, but the mother recovered after conservative treatment. Another patient at 40 weeks of pregnancy was also treated conservatively and both the fetus and the mother survived. Brain CT scan findings differed between these two eclampsia patients; local brain edema for the second patient and generalized brain edema for the first patient. Thus more active application of brain CT scan is recommended in managing pregnant patients with convulsions.

The extra-anatomical bypass formation and the exclusion of thoracic aortic aneurysms by the "paired clamp method" applied to the thoracic aorta of mongrel dogs, and the development of hind leg paralysis was studied experimentally in relation to the ratio between the mean excluded cavity pressure and the mean aortic pressure ratio (EA-ratio). The relationship between thrombus formation in the excluded cavity and the EA-ratio was also studied. Animals were divided into 4 groups: Group 1 underwent the cross-clamping of the descending thoracic aorta for 8 min; Group 2 underwent exclusion of the entire thoracic aorta under permanent bypass; Group 3 underwent ligation of 2/3 of the proximal intercostal arteries which branched from the excluded thoracic aorta; and Group 4 underwent division of the excluded thoracic aorta into 3 parts by ligation. No animals in group 1 developed paralysis. When EA-ratios were higher than 0.48, animals in groups 2 and 3 were not paralyzed, whereas all but 1 animals with EA-ratios lower than or equal to 0.48 were paralyzed. There was statistically significant difference between the EA-ratio of the non-paralyzed animals and that of the paralyzed animals in groups 2 and 3. Four out of 5 animals in group 4 were paralyzed. However, there was no statistically significant difference between the EA-ratio in these 4 paralyzed animals and that in the non-paralyzed animals in groups 2 and 3. When the EA-ratio was lower than or equal to 0.59, all but 1 excluded cavities of groups 2 and 3 animals were fully thrombosed 7 or 8 days after the operation. None of these animals showed the aggravation of the paralysis during the observation period and, conversely, the paralysis of almost all animals was ameliorated. These results suggested that the EA-ratio is useful in predicting the development of paralysis and thrombus formation in the excluded cavity after the operation of thoracic aortic aneurysms by the "paired clamp method".